An electrophysiological examination will be made of the subcellular mechanism underlying the release of neurotransmitter from motor nerve endings. The experimental procedure will employ a newly developed technique for directly estimating the quantal release parameters, m (quantal content), n (available store), and p (probability of release). These parameters, which reflect the major subcellular events responsible for release, will be examined under a variety of experimental conditions. By applying drugs with well-documented actions (e.g., prolongation of the nerve action potential), it should be possible to pharmacologically distinguish the contribution or effect of the events involved in the sequence of excitation-secretion coupling. These studies should not only clarify the mechanism of transmitter release but should also act to pinpoint the intracellular sites of action of the various drugs acting at the nerve terminal.